CA2797247A1 - Methods and uses of tie2 binding and/or activating agents - Google Patents

Methods and uses of tie2 binding and/or activating agents Download PDF

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CA2797247A1
CA2797247A1 CA2797247A CA2797247A CA2797247A1 CA 2797247 A1 CA2797247 A1 CA 2797247A1 CA 2797247 A CA2797247 A CA 2797247A CA 2797247 A CA2797247 A CA 2797247A CA 2797247 A1 CA2797247 A1 CA 2797247A1
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peptide
tie2 binding
tie2
chain
seq
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CA2797247C (en
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Paul Van Slyke
Daniel Dumont
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Sunnybrook Health Sciences Centre
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1891—Angiogenesic factors; Angiogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/515—Angiogenesic factors; Angiogenin
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2217/00—Genetically modified animals
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
    • A01K2217/203—Animal model comprising inducible/conditional expression system, e.g. hormones, tet
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2227/10—Mammal
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0368—Animal model for inflammation
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0387—Animal model for diseases of the immune system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

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  • Chemical & Material Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The present disclosure provides methods and uses of Tie2 binding and/or activating agents. In particular, the present disclosure provides methods and uses for inhibiting the expansion of colony forming unit-granulocytes, reducing eosinophils and/or basophils, for treating allergic disease or response or eosinophil/basophil associated condition and for reducing inflammatory cytokine and/or chemokine levels.

Claims (44)

1. A use of a Tie2 binding and/or activating agent for inhibiting the expansion of CFU-G cells in a cell or animal in need thereof.
2. The use of claim 1, for reducing eosinophils and/or basophils in the animal in need thereof.
3. The use of claim 1 or 2 for treating allergic disease or response in the animal in need thereof.
4. The use of claim 3 for treating atopic disease.
5. The use of claim 4, wherein the atopic disease is atopic dermatitis, asthma or allergic rhinitis.
6. The use of claim 5, for treating atopic dermatitis.
7. The use of claim 5, for treating asthma.
8. The use of claim 2 for treating a condition associated with eosinophils and/or basophils in the animal in need thereof.
9. The use of claim 8, wherein the condition associated with eosinophils and/or basophils is leukemia of eosinophil and/or basophil origin.
10. The use of claim 8, wherein the condition associated with eosinophils and/or basophils is inflammatory bowel disease.
11. The use of claim 8, wherein the condition associated with eosinophils and/or basophils is a parasitic infection.
12. The use of any one of claims 1 to 3 for reducing inflammatory cytokine and/or chemokine levels in the animal or cell in need thereof.
13. The use of claim 12, wherein the inflammatory cytokine and/or chemokine levels comprise serum levels.
14. The use of claim 12 or 13, wherein the inflammatory cytokine and/or chemokine comprises at least one of eotaxin, IL-17, MIG, IL12/IL23 (p40), IL-9, MIP-1 a, MIP-1 b, RANTES, TNF-.alpha., IL-1.beta., IL-5, IL-13, and MCP-1.
15. The use of claim 14, wherein the inflammatory cytokine and/or chemokine comprises IL-17, MIG, IL12/IL23 (p40), IL-9, MIP-1a, MIP-1b, RANTES, TNF-.alpha., IL-1.beta., IL-5, IL-13, and MCP-1.
16. The use of claim 14, wherein the inflammatory cytokine and/or chemokine comprises eotaxin.
17. The use of any one of claims 1 to 16, wherein the Tie2 binding and/or activating agent comprises angiopoietin-1 or a nucleic acid encoding angiopoietin-1.
18. The use of any one of claims 1 to 16, wherein the Tie2 binding and/or activating agent comprises a blocking antibody against angiopoietin-2.
19. The use of any one of claims 1 to 16, wherein the Tie2 binding and/or activating agent comprises a Tie2 binding peptide monomer.
20. The use of claim 19, wherein the Tie2 binding and/or activating agent comprises a multimeric form of the Tie2 binding peptide monomer.
21. The use of claim 20, wherein the multimeric form is a tetramer.
22. The use of claim 20, wherein the multimeric form is a dimer.
23. The use of claim 20, wherein the multimeric form comprises six, eight, ten or twelve units of the Tie2 binding peptide monomer.
24. The use of claim 20, wherein the Tie2 binding peptide monomer comprises a structure: A-B, wherein A comprises a Tie2 binding peptide and B
comprises a spacer, wherein the multimeric form is created by covalent linkage of multiple Tie2 binding peptide monomers via the spacer B.
25. The use of claim 24, wherein B comprises polyethylene glycol (PEG).
26. The use of any one of claims 19-25, wherein the Tie2 binding peptide monomer comprises a T7 peptide as shown in SEQ ID NOs: 1 or 2.
27. The use of any one of claims 19-25, wherein the Tie2 binding peptide monomer comprises a GA3 peptide as shown in SEQ ID NOs: 3 or 4.
28. The use of any one of claims 19-25, wherein the Tie2 binding peptide monomer comprises a peptide selected form the group consisting of a T4 peptide, a T6 peptide and a T8 peptide as shown in SEQ ID NOs:5-10.
29. The use of claim 20, wherein the multimeric form is a dimer, comprising:
(a) a first peptide chain; (b) a second peptide chain; and (c) a linking moiety connecting said first and second peptide chains, wherein said peptide dimer binds to and activates the Tie2 receptor.
30. The use of claim 29, wherein the first peptide chain is a T7 peptide (SEQ
ID NOs: 1 or 2).
31. The use of claim 29 or 30, wherein the second peptide chain is a T7 peptide (SEQ ID NOs: 1 or 2).
32. The use of any one of claims 29 to 31, wherein the linking moiety comprises one or more water soluble polymers covalently bound to the first peptide chain and the second peptide chain.
33. The use of claim 32, wherein the one or more water soluble polymers are linear polymers.
34. The use of claim 32, wherein the water soluble polymer is a polyethylene glycol (PEG).
35. The use of claim 20, wherein the multimeric form comprises a peptide tetramer, comprising: (a) a first peptide chain; (b) a second peptide chain;
(c) a third peptide chain; (d) a fourth peptide chain; and (e) a linking moiety connecting said first, second, third and fourth peptide chains, wherein said peptide tetramer binds to and activates the Tie2 receptor.
36. The use of claim 35, wherein the first, second, third and fourth peptide chains are T7 peptides (SEQ ID NOs: 1 or 2).
37. The use of claim 35 or 36, wherein the linking moiety comprises one or more soluble polymers covalently bound to the first, second, third and fourth peptide chains.
38. The use of any one of claims 35 to 37, wherein the water soluble polymer is a branched chain water soluble polymer.
39. The use of claim 38, wherein the water soluble polymer is a branched chain polyethylene glycol (PEG).
40. The use of claim 39, wherein the PEG has a molecular weight in a range of about 3,000 Daltons to about 50,000 Daltons.
41. The use of any one of claims 1 to 40, wherein the agent is administered topically.
42. The use of any one of claims 1 to 40, wherein the agent is administered systemically.
43. The use of any one of claims 1 to 40, wherein the agent is administered intranasally or by inhalation.
44. The use of any one of claims 1 to 43, wherein the subject is human.
CA2797247A 2010-04-28 2011-04-28 Methods and uses of tie2 binding and/or activating agents Active CA2797247C (en)

Applications Claiming Priority (3)

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US32893210P 2010-04-28 2010-04-28
US61/328,932 2010-04-28
PCT/CA2011/000473 WO2011134056A1 (en) 2010-04-28 2011-04-28 Methods and uses of tie2 binding and/or activating agents

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CA2797247A1 true CA2797247A1 (en) 2011-11-03
CA2797247C CA2797247C (en) 2019-10-22

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Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150050277A1 (en) 2013-03-15 2015-02-19 Aerpio Therapeutics Inc. Compositions and methods for treating ocular diseases
MY171945A (en) * 2013-03-15 2019-11-08 Aerpio Therapeutics Inc Compositions, formulations and methods for treating ocular diseases
CA2909080C (en) 2013-04-11 2022-07-26 Sunnybrook Research Institute Methods, uses and compositions of tie2 agonists
WO2016029125A1 (en) * 2014-08-22 2016-02-25 The Regents Of The University Of Michigan Peptide reagents and methods for detection and targeting of dysplasia, early cancer and cancer
CN110225922B (en) * 2017-01-13 2023-09-12 血管免疫治疗公司 Agents for promoting angiogenesis and methods and uses thereof

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Publication number Priority date Publication date Assignee Title
WO2006005361A1 (en) * 2004-07-13 2006-01-19 Centre National De La Recherche Scientifique Peptides liable to bind to the tie2 receptor, nucleic acids encoding them, and their uses
CA2581769C (en) 2004-09-28 2014-03-11 Genexel-Sein, Inc. Methods of using chimeric coiled-coil molecule
PT2076290T (en) 2006-10-27 2017-01-17 Sunnybrook Health Sciences Center Multimeric tie 2 agonists and uses thereof in stimulating angiogenesis
MX2010008099A (en) * 2008-01-28 2010-08-04 Medimmune Ltd Stabilized angiopoietin-2 antibodies and uses thereof.
WO2009114539A2 (en) 2008-03-10 2009-09-17 University Of Louisville Research Foundation Neuroprotective integrin-binding peptide and angiopoietin-1 treatments
US8529943B2 (en) 2008-07-21 2013-09-10 Compugen Ltd. Angiopoietin derived peptides

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